Dr Tom McLoughlin Senior InspectorOffice of Climate Change, Licensing & Resource Use EPA
Regulations
S.I. No 73 of 2001 (Contained Use of GMOs)
transposes Directive 98/81/EC amending Directive
90/219/EEC-Contained use of GMM.
S.I. No 54 of 2004 (Transboundary Movement)-Reg.
1946/03
Regulation of GMOs in Contained Use facilities in Ireland by the EPA
Aims and Objectives
Government Policy Definitions Interpretations Legislation Obligations on the GMO user Classification of GMM Risk Assessment Requirements for GMM/GMO Notifications Biological Safety Committee/BSO Cartegena Protocol Enforcement by the EPA Duties and Power of the Agency Future Trends
Definitions
Micro-organism means ‘any microbiological entity, cellular or non cellular, capable of replication or of transferring genetic material, including viruses, viroids, animal and plant cells in culture’
Genetically Modified Micro-organisms-GMM• bacteria, • viruses, • fungi, • plant & animal cells, capable of replication or of transferring genetic material inwhich the genetic material has been altered in a way that does not occur naturally by mating or natural recombination.
Definitions
Genetically Modified Organisms means any organism in which the genetic material has been altered in a way that does not occur naturally by mating or natural recombination or by a combination of both
e.g. plants & animals
GMOs inclusive of Genetically Modified Micro-organisms (GMMs).
Definitions
Contained use ‘any activity in which organisms are geneticallymodified or in which such organisms are cultured, stored, transported, destroyed, disposed of or used in any other way and for which specific containment and other protective measures are used to limit their contact with the general public and the environment'.
Containment measures/barriers can be physical, biological or chemical or a combination of these.
Contained Use (CU) Directive 98/81/EC amending 90/219/ECCObjectives of Directive:Preventive action be taken - protect the environment & human health
CU of GMMs - classified in relation to the risks - present for human health & environment Classification - based on RA Containment and other protective measures – correspond - classification of CU Adopt appropriate measures for the disposal of waste - from CU of GMM
GMO (Contained Use) Regulations, 2001-S.I. No. 73 of 2001 (60 Articles + 8 Schedules)
Part I - General Part II - Contained use of GMMs Part III - Contained use of GMOs Part IV - Fees & charges Part V - Enforcement & regulation Part VI - Advisory Committee on GMOs, Monitoring & Reporting etc.
Obligations
Article 5- A user or any other person carrying out an activity involving a contained use shall ensure that all appropriate measures are taken to avoid adverse effects on human health and the environment.
Article 13-Before commencing a Contained Use- RA must be carried out –human health and the environment-which may be associated with such use.
What we don’t want…
“Probe af ter Scots student’s smallpox accident”
The Sunday Post17th December 2000
“SARS spreads in China: I nvestigation launched into lab safety.”27 April 2004 Nature Science Update
'Pirbright link' to farm outbreak
What is Regulated/Not Regulated?
Techniques of Genetic Modification - cloning vectors -plasmids & viruses-direct introduction - micro-injection, macro-injection and micro-encapsulation-cell fusion
Techniques which are not considered to be GMO - In vitro fertilisation-conjugation, transduction, transformation, mutagenesis, cell fusion, self cloning
Oct 2007 - Working Group to be set at EU level up to look at ‘newer’ techniques of GE to ascertain if they should be included or excluded from the remitt of EU Directives-CU/DR?
Exemption of safe organisms - Annex II, Part B?
Classification of GMM based on Risk Assessment
• Activities classified into 1 of 4 classes (Class 1, 2, 3, or 4)Class 1 - activities of no or negligible risk, Containment Level 1 (CL1) is appropriate Class 2 - activities of low risk, CL2Class 3 - activities of moderate risk, CL3Class 4 - activities of high risk, CL4
• Classification is based on Risk Assessment (Art. 13)• Appropriate level of containment required to control risk to
human health and the environment.
15252
0
049
8
Class 1 Class 2 Class 3 Class 4 GMO Deliberate Release
Register of GMO users in Ireland – October 2007
• 261 registered users
• 78% contained use consents (Class 1 & 2)
58%20%
Elements of Risk Assessment
1. Provisional allocation to Class 1, 2, 3 or 4 as per DIRECTIVE 2000/54/EC –Biological agents at work
2. Identification of potentially harmful effects associated with: Recipient Micro-organism Genetic insert Vector Donor micro-organism Resulting GMM
3. Assessment of potentially harmful effects occurring 4. Assign appropriate containment level (CL 1, 2, 3 or 4) and other protective
measures to control risk5. Review and confirm classification in light of completed assessment
Containment Levels and Measures (4th Sched)
Table 1A – minimum requirement for contained use of a GMM in a laboratory
Table 1B – in addition to Table 1A contained use of a GMM in plant growth facilities
Table 1C – in addition to Table 1A contained use of a GMM in animal units
Table II – minimum requirements for GMM in facilities other than those covered
by tables 1A, 1B or 1C
GMP (Good Microbiological Practices)
GOSH (Good Occupational Safety and Hygiene)
Training, Containment equipment & Special Installation Design.
Advice - Biological Safety Committees, BSO
Containment Measures
GMP & GOSH
Keep workplace & environmental exposure - GMM - lowest practicable level; Exercise engineering control measures - source & supplement - protective clothing & equipment; Test & maintain control measures/equipment; Test for presence of GMM outside-primary physical containment; Provide training of personnel; Establish biological safety committees/subcomm. Formulate & implement local codes of practice- safety of personnel, display biohazard signs;
GMP & GOSH-cont.
Provide washing & decontamination facilities - personnel; Adequate records; written SOP’s to ensure safety; Effective disinfectants - disinfection procedures - spillage of GMMs; Safe storage - contaminated laboratory equipment & materialsProhibit eating, drinking, smoking, application of cosmetics or storage of food for human consumption -work area; prohibit mouth pipetting.
GMM Notification Requirements
• Art. 16 states that a premises shall not be used for the first time unless• a notification has been submitted by user to EPA• a consent for such use has been granted by EPA• compliance with consent conditions
GMM Notification Requirements
GMM notification
First time use of a premises
Subsequent contained use
Class 1, 2, 3 & 4.
Class 2, 3 & 4.
+
GMM Notification requirements
First time use of the premises Subsequent contained use
Class 1 •Information under Part A of 5th Schedule •Risk Assessment •Fee €250
Class 2 •Information under Part A of 5th Schedule •Fee €1,250
•Information under Part B, 5th Schedule•Risk Assessment •Fee €625
Class 3 •Information under Part A of 5th Schedule •Fee €3,000
•Information under Part C, 5th Schedule•Risk Assessment •Fee €1,500•Public notice
Class 4 •Information under Part A of 5th Schedule •Fee €15,000
•Information under Part C, 5th Schedule•Risk Assessment •Fee €7,500•Public notice
GMM Notification Requirements
Timeframe for decisions
First time use of a premises• Class 1/2 - 45 days• Class 3/4 - 90 days
Subsequent use of a premises• Class 2 – 10 days • Class 3/4 - Notifier may not proceed without the EPA’s prior
approval and the EPA must revert within 45 days.
Clock Stoppage
GMM Notification Requirements
Consents (Article 26) EPA will • issue consent with or without conditions, or,• refuse consent
Fees (8th Schedule) Receipt of fees validates notification Refund/waiver of up to 50% of fees payable (Article
48)
GMM Notification Requirements
Annual Reporting
User is required to carry out and maintain Risk Assessments(RAs) and to submit to EPA with annual report.
INFORMATION REQUIRED -NOTIFICATION FOR FIRST TIME USE OF PREMISES FOR CONTAINED USE - ARTICLE
16Name of user, persons responsible for supervision & safetyTraining & qualifications of persons - supervision & safetyDetails - biological committees/subcommitteesAddress & general description of premisesDescription of the nature of the workClass of the contained useClass 1 GMM - a summary of RA - Article 13Information on waste managementRelevant fee - 8th Schedule
Information required for a Class 2 contained use - Article 18
Date of submission of the notification - Article 16 Names of persons-supervision & safety & information - training & qualifications Recipient, donor &/or parental micro-organism(s) used & the host -vector Source(s) & intended function(s) of the genetic material - used in modification Identity & characteristics of the GMM Purpose of contained use - expected results Approximate culture volumes - used Description of containment measures, information about waste Management - wastes generated – treatment, final form & destination A summary of the RA - Article 13 Information - CA to evaluate any emergency response plans - Article 30. Relevant fee - 8th Schedule
GMO Notification Requirements
Notification of Contained Use for a GMO (GM plants/animals) must contain
• Risk Assessment (Article 36(2), Part II of 7th Schedule)• Information set out in Part I of 7th Schedule• Fees – no requirement• Activity may commence 45 days after submission of
notification• The EPA is not required to issue consent• Annual reporting applies• Guidelines
Enforcement
Under Article 26 of the CU Regulations the EPA can issue a consent with or without conditions or refuse consent.
Enforcement - Article 56 –‘The Agency shall carry out, cause to be carried out or arrange for such monitoring, inspections ….’
To ensure - users comply – conditions - licence To ensure - risks to human health & environment -
managed properly - promote high standard of biological safety
Allay public concerns Regulator of GM technology - 3rd level; biopharma industry
Site Inspection
What we look for (use a checklist that was agreed at the European Enforcement Project CU) General Information re the premises Containment measures in place
Restricted access Biohazard signs Procedures / RA Training / training records Class of MSC /date of last validation Personal protective measures GMP / GOSH Handwashing facilities Segregation of write up area General observations
Site Inspection continued
GMM Storage Location /in lab?/ elsewhere? / inventory
Waste Inactivation Location of autoclave relative to lab Last date of validation Procedure for decontamination of
Solid waste Liquid waste Sharps
Procedure for treatment of spillages Decontaminating agents Procedure for reporting of accidents / incidents
Are GMOs/GMMs used for teaching purposes?
Enforcement actions
Site inspection is followed up with Site inspection report Letter of non-compliance to registered user, where applicable, for
example, Annual reporting Where user has relocated activity and has not informed the Agency SOPs Non-notified activity BSC-management structure Prosecution of Offences
HC injunction Notice to Take Measures
Duties & Power of the EPA
• Review of contained use activities• Enforce Regulations - site inspections, compliance
with consent conditions• EPA - require modification, suspension or termination• Report - Minister-performance of functions • Inform the EU Commission of accidents• Notice to take measures • Prosecution of offences• High Court Injunction
Cartegena Protocol
UN legislation to protect biodiversity – EU RegulationCovers all LMO’s transboundary movement outside the EU
Reguirements for Contained Use:Exporters need to provide documentation:Labelling-that it contains or consists of a GMOUnique code, if availableRA relating to the safe handling, storage and transportContacts for further information
Help and Guidance
www.epa.ie - under ‘What we do/Licensing and Permitting/GMOs’Licensing process explainedContained Use of GMMs and GMOs,Risk assessment - examplesWho should apply - proceduresAnnual reporting guidanceLegislation
Future Trends
Move to use replicating viral vectors with altered tropism/tissue specificity/ immune evasionIncreasing development of viral chimerasReverse genetics of multi-segmented ds RNA viruses (e.g., Blue-tongue, Rotavirus)Biopharming-to produce human medicines?Drivers for change - e.g., SARs, Influenza H5N1, Climate Change - Blue tongue
Concluding remarks
The overriding concern of the EPA in the implementation of the GMO Contained UseRegulations is to ensure that their use does nothave an adverse effect on human health or theenvironment.
